In these studies a new kind of irreversible enzyme inhibitor is developed to allow for the specific and irreversible inhibition of certain enzymes involved in neurotransmitter amine metabolism. We propose to study the biochemical, pharmacological and behavioral effects of these inhibitors. The irreversible inhibitors introduced are of an extraordinary specific type containing hidden reactive functional groups which require the enzyme by its specific mode of action to unmask them. Thus, the enzyme catalyzes its own irreversible inactivation. The inhibitors are introduced to specifically and irreversibly inhibit the various monoamine oxidases, histaminase, glutamic acid decarboxylase, and gamma aminobutyric acid-alpha-ketoglutamic acid transaminase. With these inhibitors we propose to uncover the precise physiological role of the different neurotransmitter amines in addition to using them as an aid in the purification of certain of these enzymes. We plan to study the behavioral effect of the inhibitors along with using them to study interplay between the various neurotransmitters. In addition, we plan to locate the site of action of enzymes such as glutamic acid decarboxylase in the neuron. And finally we are going to study the mechanisms of action of the inhibitors as they relate to the mechanisms of action of the enzymes involved in neurotransmitter metabolism. BIBLIOGRAPHIC REFERENCES: Rando, R.R.: On the mechanism of action of antibiotics which act as irreversible enzyme inhibitors. Biochem. Pharmacol. 24: 1153 (1975). Rando, R.R.: Mechanisms of action of naturally occurring irreversible enzyme inhibitors. Acc. Chem. Res. 8: 281 (1975).